This is a revised application for the third competitive renewal of the Cleveland Training Program in Cardiovascular Research. The goal of this program continues to be to the provision of outstanding long-term training in cardiovascular basic research to six promising predoctoral trainees and five highly qualified M.D.s or Ph.D.s who intend to pursue academic research or other science leadership careers. The training focuses on basic mechanisms of cell physiology, biochemistry and biophysics pertinent to heart and cardiovascular disease, in particular, to arteriosclerosis, hypertension, ischemic heart diseases, coronary artery diseases and arrhythmia. The program offers a broad repertoire of experimental approaches and problems of investigation in cardiac and smooth muscle cells both under physiological and pathological conditions. The major strengths of the proposed training are the breadth of research offered to trainees, ranging from the anesthetized animal to protein structure and proteomics--and a positiveand highly interacting, nurturing environment. Outstanding research opportunities exist in cardiac electrophysiology, cardiac metabolism, membrane transport and intracellular signaling, genetics and structural biology. The training faculty on this application consist of 19 interactive, active and well-funded faculty in several departments at all five major academic institutions in Cleveland: Case Western Reserve University School of Medicine, MetroHealth Medical Center, University Hospitals of Cleveland, the Cleveland Veterans Affairs Medical Center and The Cleveland Clinic Foundation. They represent a good mix of senior investigators with demonstrated training records and promising new junior faculty. The facilities of the training faculty comprise 50,000 square feet of research laboratories and $9 million in extramural research dollars. The trainees have available a dozen excellent graduate-level courses, a weekly variety of seminars and journal clubs and other novel educational experiences. An effective mechanism of administration and governance is in place to assure recruitment, admission, quality control and career placement counseling for the trainees. During the previous funding period all the positions were competitively filled. The trainee record in terms of publications, training experience and post-training placement continues to be a major strength of this program. This revised renewal application incorporates newly recruited faculty in several institutions while providing a tighter focus on cardiovascular research and expanded training opportunities in areas of imaging, electrophysiology and proteomics. This program has been the major collegial interdepartmental and interinstitutional focus for basic cardiovascular research in Cleveland. The proposed renewal will continue to facilitate interaction among faculty and trainees and expand the culture and training excellence in cardiovascular research.